Our overall goal is to develop comprehensive technologies that allow for cell-specific delivery of small molecule therapeutics, genes, or proteins in vivo. We have employed phage display libraries to isolate peptides that bind to and invade specific cell types. This approach works with a wide variety of cell types and we have isolated targeting peptides for 20 different cell types. These peptides display remarkable cell- type specificity. In other words, the isolated peptides show selectivity for the cell type they were selected against in comparison to other cell types, even those that are closely related. We propose to identify peptides that bind to and mediate cellular uptake in to critical cells of the immune system, namely, T-cells, B-cells, and dendritic cells. Targeting immune cells in vivo represents a major challenge in medicine, and there are many medical applications in which cell-specific delivery agents would be advantageous. Furthermore, the immune system provides us with convenient biological outputs so that the effects of targeting in vivo can be easily followed. As targeting peptides are identified, they will be utilized to deliver biologically active molecules to the cells both in vitro and in vivo. We will use the peptides in the context of the phage as well as develop peptide scaffolds that can be used as replacements for or in conjunction with the selected phage. Achieving our goals will impact vaccinology and immunomodulation therapies as well as solving many general problems in the area of cell-specific delivery in vivo.